CUBE GUIDELINESSIE Guidelines Methodology Manual

Version 1.1 – January 2015

Sommario

1 – Mission and core principles....................................................................................................................4

1.1.Premise ......................................................................................................................................4

1.2 Objectives..................................................................................................................................4

1.3 Core principles..........................................................................4

2 – Actors........................................................................................................................................................6

2-1 General organization................................................................................................................6

2-2 Strategic Committee.................................................................................................................6

2-2-1 Members.................................................................................................................................6

2-2-2 Duties......................................................................................................................................6

2-3 Methodology Committee........................................................................................................6

2-3-1 Members.................................................................................................................................6

2-3-2 Duties......................................................................................................................................6

2-4 Working Groups........................................................................7

2-4-1 Members.................................................................................................................................7

2-4 Extended Committee...............................................................................................................7

3 – The Process...............................................................................................................................................8

4 – Topics......................................................................................................................................................11

5 – Harmonization.......................................................................................................................................12

6 – Original recommendations...................................................................................................................14

7 – Dissemination.........................................................................................................................................15

8 – Updating.................................................................................................................................................15

9 – Conflict of interest policy......................................................................................................................15

10 – References.............................................................................................................................................19

11 – Appendix 1- AGREE checklist............................................................................................................19

12 – Appendix 2- Sources for guidelines search.......................................................................................20

12

1 – Mission and core principles

1.1.Premise The development and updating of high-quality practice guidelines require substantial resources,and most organisations are under pressure to produce more guidelines in a shorter time with increasingly limited resources. Moreover, despite evidence that routine application of clinical practice guidelines effectivelyimproves the quality of health-care, utilization of guidelines is scarce due to several reasons suchas the format (length and textual versus graphical/interactive presentation, portability), clearity,ambiguity, comprehensiveness, regular updating, inconsistency with other guidelines, availabilityof tools (checklists, calculators, patient information material) for the clinical practice.

1.2 ObjectivesThe new SIE guideline project has a doublefold aim:

- to provide regularly updated high-quality guidelines taking advantage of existing highquality international guidelines

- to enhance the efficient use of high-quality guidelines through innovative disseminationtools

1.3 Core principlesThe core methodologies on which the new guidelines project will be based are ADAPTE andGRADE.Both the methods are based on the PICOT paradigm. PICOT stays for Patient, Intervention,Comparator, Outcome, and Time. PICOT is the format a clinical question needs to have in order tomake it answerable with evidence-based methodsMore specifically according to ADAPTE, the harmonization process of existing guidelines willbe based on the following core principles:

- Respect for the evidence-based principles of guideline development- Reliable and consistent methods to ensure the quality of the adapted guideline- Participative approach, involving all key stakeholders, to foster acceptance and

ownership of the adapted guideline- Explicit consideration of context during adaptation to ensure relevance for local

practice- Transparent reporting to promote confidence in the recommendations of the adapte

d guideline- Accountability to the primary guideline sources

As endorsed by the international GRADE working group, the classification of practicerecommendations is defined as strong (Grade 1) or weak (Grade 2), according to the balancebetween benefits, risks, burden, and cost, and the degree of confidence in estimates of benefits,risks, and burden. The system classifies quality of evidence (as reflected in confidence in estimates

of effects) as high (Grade A), moderate (Grade B), or low (Grade C) according to factors thatinclude the risk of bias, precision of estimates, the consistency of the results, and the directness ofthe evidence.

In order to enhance the implementation of the best available clinical evidence SIE aims atproviding Italian hematologists with “portable”, “ interactive” and comprehensive high qualityguidelines. Since guidelines retain a relevant legal and economic value, SIE also aims at providingstakeholders and judges with appropriate tools for judging appropriate vs inappropriate practiceand for approval/funding priorization.The project has been named “CUBE”, just to remind the multiple facets of the planned guidelines.

2 – Actors

2-1 General organizationThe Task Force devoted to Guidelines includes a Strategic Committee, a Methodology Committeeand a Scientific Committee. An Extended Committee provide the Task Force feedback and allowsvalidation of guidelines.

2-2 Strategic Committee

2-2-1 MembersIt includes SIE President plus four members selected by the President himself amongpast-presidents and senior leaders of national and international research networks.

2-2-2 DutiesThe strategic committee is responsible for:

a) Selecting members of the area-specific Scientific Committee

b) Selecting the leaders of the Methodology Committee

c) Supervising on Conflict of Interest

d) Keeping relationships with SIE

e) Planning guidelines updates

2-3 Methodology Committee

2-3-1 MembersThe Methodology Committee is composed by experts in the field of clinical methodology. Thecommittee may comprise up to 10 members and is organized into two Methodology WorkingGroups (MWG), each with a leader and members selected by the leader: West MWG and EastMWG.

2-3-2 DutiesThe Methodology Committee is in charge of:

a) Educating members of the Scientific Committees

b) Coordinating topic/issue selection

c) Conducting guidelines retrieval and critical appraisal

d) Elaborating tabular and algorithmic representation of guideline content

e) Coordinating guideline harmonization

f) Formulating PICOTs for orphan areas

g) Revise literature GRADE

h) Yearly literature scan

2-4 Working Groups

2-4-1 MembersThe Area-Specific Working Groups comprises experts in specific areas of the hematology. EachArea-specific Working Group is coordinated by a member designed by the Steering Committeeand is committed to:

a) Selecting of domains of each guidelines

b) Priorizing of issues

c) Identifying the aims of each guidelines

d) Selecting the Critical Outcomes for each PICOT

e) Validating PICOT-based recommendations

f) Validating recommendation algorithm derived from harmonization of guidelines

g) Driving national peer-review (Extended Committee)

h) Implementing legal and economic aspects of the guidelines

i) Writing textual items for Web and paper editing

j) Annual updating based on peer-review

2-4 Extended CommitteeThe Extended Committee is composed by 5 SIE members elected by the Working group members of each Area.

They are in charge of:

− Validation of the whole guideline

− Final approval in case of lack of concordance in the Working group members

3 – The Process

The whole guideline elaboration process was designed according to GRADE and ADAPTE standards.

The starting phase for the preparation of each guideline follows the flow chart depicted below:.

Where:SWG = Scientific Working Group. MWG stays for Methodology Working Group.toPIc = each topic identifies a population (i.e. naïve patients with FCL) and a class of interventions (i.e. treatment)

The detailed process that will be adopted will implies the following steps:

- Identification and development of each single PI (Population and class of intervention)

-

Figure 3 – Details of the process from PI flow to PICOT elaboration.

Figure 4 – Final results of guideline retrieval. Recommendations derived from selected guidelines are compared for each PICOT.,

Figure 5 – Harmonization final phase : management of AAIO recommendations derived from retrieved guidelines.

Figure 6 – Different type of clinical actions represented in the interactive flow-chart that graphically

represents the guideline (for web and smartphone).

4 – TopicsThe clinical domains as selected by the Strategic Committee:

a) Acute leukemia

b) Chronic myeloid leukemia

c) Ph-negative chronic myeloproliferative disorders

d) Chronic lymphocythic leukemia

e) Lymphomas

f) Multiple myeloma and related-disorders

g) Myelodysplastic syndromes

h) Thrombosis and haemostasis

i) Support therapy

j) Infections

k) Red blood cell disorders

The Scientific Committee of each area selects the topic to be addressed during the current year by the following analythic hierarchy process:

− Listing of possible topics− Listing of values for priorization− Pairwise comparison of values (scores -9 to +9)− Geometric means allow to calculate a rank− Identification of three major values− Calculation of percent weight of the three major values

− Pairwise comparison of topics according to each value (scores -9 to +9)− Geometric means are calculated and weighted against the values relative weights− Ranking of topics and selection − Domain refinement of the selected topic

Domain refinement includes consensus on the definition of disease and the clinical setting (i.e. primary idiopathic thrombocythopenia in adults). Refinement might also restrict the domain to the sole therapeutic or the sole diagnostic process.

5 – HarmonizationAccording to the ADAPTE methodology, for each selected topic, a search for existing guidelines should be conducted in a standard list of repositories (see table xx – ADAPTE Manual).

5-1 SYSTEMATIC SEARCH FOR GUIDELINES

The 46 databases listed in Appendix 2 will be systematically searched with progressive and explicit keywordrefinement.

5-2 CRITICAL SELECTION OF RETRIEVED GUIDELINES

Clinical Practice Guidelines will be identified by three criteria, all of which need to be fulfilled: 1) list of prescriptive recommendations for health-care workers; 2) association of recommendations with scored quality of evidence and/or strength of the recommendation; 3) endorsement by an institution/scientific society/agency.

Each retrieved guideline will be described by a checklist including:

- Title

- Authors (experts)

o Multidisciplinary panel?

- Institution

o Network

o International (or “gold-standard”) Scientific Society

o National Scientific Society

o Health-care Agency

o Hospital

- National or international?

o Country

o International

- Language(s)

- Publication date

o Updates

- Systematic review of evidence performed?

o End of literature search date

- Peer review performed?

- Population

- Setting

- Intervention

The selection process starts by publication date: no guideline published before the year 2000 without subsequent revision will be selected; guidelines based on literature review ended before 2010 (without subsequent updates) will be selected only if international or peer-reviewed.

Next selection step regards adequacy of population, setting and intervention to the profile defined by the Scientific Committee.

Finally, English language is required for the guideline selection.

5-3 CRITICAL APPRAISAL OF GUIDELINE QUALITY

AGREE items are checked for each selected guidelines by two independent reviewers (Appendix 1). Inconsistent score are discussed face-to-face.

5-2 TABULAR REPRESENTATION OF GUIDELINE CONTENT

According to ADAPTE methodology manual, the content of guideline recommendations is reported in a synopsis table (matrix) indexed with one PICOT per row and one guideline per column.

The guidelines achieving highest AGREE scores will be used a referral backbone: clinical questions will be formerly extracted from it and subsequently integrated with those present in other guidelines.

5-3 ALGORITHMIC REPRESENTATION OF GUIDELINES CONTENT

A flow-chart of the recommended sequential actions is developed for each selected guideline. An algorithmis built through the guideline editor GUIDE, a JAVA-based tool developed by the Compute Sci Dpt of Pavia University. The editor allows for different representation of info-gathering actions, therapeutic decision actions, monitoring actions…… The editor also tacks the ontologies used by the guideline.

5-4 IDENTIFICATION OF CONSISTENT RECOMMENDATIONS

Consistency of recommendations is checked in synopsis tables. However, only consistent recommendationsthat the Scientific and Methodology WG judge to be adequately updated are ADOPTED.

The Methodology WG proposes the most adequate strength of recommendation and level of evidence to be associated with consistent recommendations, in case of consistent content but inconsistent weighting.

5-5 IDENTIFICATION OF INCONSISTENT RECOMMENDATIONS

Recommendations for a single PICOT can be slightly different among guidelines or prove some differencedue to the setting (i.e. country). These differences allow to ADAPTE the recommendations. On converse,huge inconsistencies due to different updating of guidelines or to different weighting of outcomes, in spiteof the same evidence base, require to be addressed more carefully. If inconsistency derives from differentupdating, the recommendation provided by the most recently updated guideline can be chosen. Otherwisethe PICOT needs to be fully exploited de novo.

5-6 IDENTIFICATION OF ORPHAN/CRITICAL TOPICS

Orphan topics are identified based on the algorithmic representation of guidelines or a-priori by theScientific WG.

6 – Original recommendations

6-1 Priorization of orphan-topics and inconsistent topics:

An analythic hierarchy process allows a transparent selection of topics to be addressed through thefollowing steps:

a) Values, i.e. criteria for defining the relative importance of topics, are listed by the Scientific Committee

b) Values are compared pairwise and assigned a relative weight ranging from -9 to +9

c) Geometric means of relative weights are calculated

d) The top 3 ranked values are selected

e) Percent weight of the 3 values is calculated

f) Topics are judged pairwise according to each value (scores -9 to +9)

g) Geometric means of scores are weighted by the percent weight of each value

h) The top 3 ranked topics are selected

6-2 FORMULATION OF PICOTS

Each selected topic is formulated in the Patient-Intervention-Comparator-Outcome-Time format in order tobe addressed with the GRADE methodology. Critical Outcomes and Time Horizon relevant for therecommendation are selected by the Methodology WG and confirmed by the Scientific WG.

6-3 SYSTEMATIC REVIEW OF EVIDENCE

According to GRADE methodology, a search with specific keywords is conducted in COCHRANE LIBRARY,MEDLINE, EMBASE and the proceedings of ASH, EHA, ASCO meetings limited to the last 5 years. Selectionrules are expected to vary between areas and PICOTS. Evidence tables are produced.

6-4 ELABORATION OF RECOMMENDATIONS

Recommendations are proposed by the Methodology WG based on the evidence tables in the SecondReport. Final discussion will be held at the final meeting.

7 – DisseminationThe flow-chart elaborated by the Scientific WG will be validated during the final meeting and will providethe graphic backbone for navigation through the guideline. Contents of the flow-chart boxes will be derivedfrom PICOT-based recommendation. Adopted and adapted recommendations will be directly incorporatedinto the flow-chart, while orphan and inconsistent recommendations will need a subsequent elaboration ofnew recommendations. The flow-chart will have a color-code allowing the reader to distinguish robust /strong recommendations versus frail /mild ones and to distinguish between adopted or adaptedrecommendations and newly elaborated ones.

Those boxes of the flow-chart prompting calculation of scores, checking diagnostic criteria, checking response criteria or verifying therapy schedules will provide links to checklists and calculators in order to allow the user to integrate the guideline with his/her clinical practice by getting a full support.

A pocket guide is provided in Adobe Acrobat format to be downloadable from the web site.

8 – UpdatingEach year the Methodology Committee will be in charge of reviewing newly published/presented evidencerelevant to each developed guidelines. The Methodology Committee will select the evidence whichpotentially can trigger changes in the guideline content or structure and will elaborate a report for theScientific Committee. The Scientific Committee parallel will revise current recommendations and listsrecommendations deserving revision as well as new orphan topics to be addressed. The ScientificCommittee will revise the evidence, will update the report submitted by the Methodology Committee andwill confirm the requirement of modifications or new development of recommendations or guidelinestructure or content. A Consensus Process will select major and minor modifications. A GRADE process willbe used to address major modifications.

9 – Conflict of interest policy9.1 IntroductionThe Società Italiana di Ematologia (SIE) is committed to the very highest ethical standards in all its activities,including the development of clinical policies for management and treatment of hematological diseases.The SIE has always taken a stringent approach to ensure responsible, transparent relationships in which in-dustry support and other relevant entities have no influence on the content of any scientific or professionalmaterial developed, published and diffused under its coverage.However, the SIE do believe that that experts involved into writing committees who have relationships withindustry and other relevant entities, when transparent and properly managed, strengthens the writing ef-fort and final published document. However, part- or full-time employees of industry are prohibited fromserving as members of guideline writing committees. The following policy outlines the SIE methodology forensuring a document development process without improper bias or influence.

9.2 Scope

The SIE requires for all the expert involved in the development of guidelines the periodic disclosure of all re -lationships with industry and other entities (as defined in Section 9.4) involved in the production, market-ing, distribution or reselling of healthcare goods, services, advice or information consumed by patients, in-vestors and/or physicians. This may include relationships with government entities as well as not-for-profitinstitutions and organizations (see category definitions for details)

9.3 Relationships with Industry (RWI) Versus Conflict of Interest (COI)The SIE consider as the most appropriate the term Relationships with Industry (RWI) and other entities asopposed to the term Conflict of Interest (COI). RWI, by definition, does NOT necessarily imply a conflict. In-deed, when all relationships are disclosed with the appropriate detail regarding the type, and they are man -aged appropriately for building consensus and voting, the SIE believes that potential bias can be avoidedand the final published document is strengthened since the necessary expertise is accessible.

9.4 General Principles for Managing RWI

9.4.1 The RWI of SIEThe SIE acknowledge the relevant educative value of guideline development and diffusion among physi -cians and other healthcare operators. Therefore, guidelines preparation is core to the society educationmissions and no direct influence from industries or from a direct sponsorship is allowed on any aspect ofthem. However, according to the general principle of a responsible, transparent relationship with indus-tries and other entities bearing interests in the production, marketing, distribution of healthcare goodsand services, the SIE reserves the right to allocate for the guideline preparation, publication or diffusion,part of its own resources or unrestricted grant received to support its education activities.

9.4.2 Collecting RWIListed below is the information the SIE collects for the purposes of managing relationships with indus-try and other entities for guideline development.

9.4.3 Reporting TimeframeThe SIE requires the disclosure of all relationships with industry and other entities for the past 12months. In addition, guideline authors are discouraged from adding new RWI during the writing ef-fort and prior to publication; however, if relevant relationships are added, this information must beverbally disclosed during any conference calls or meetings, as well as added to the author disclosuretable.

9.4.4 Relationship TypeThe following definitions are used to define categories for reporting relationships with industry andother entities.

REPORT-ING CATE-

GORY

DEFINITION

Consultant

Includes relationships resulting in honoraria from a third party, gifts or other consideration, or "in kind" compensation, whether for consulting, lecturing, service on an advisory board, or for any other similar purpose inthe prior calendar year.

Speaker’s Bureau Includes compensation from speaker’s bureaus.

Ownership/ Partnership(excludingmutual diversified funds)

Includes status as any stock, stock option, ownership, partnership, mem-bership or other equity position in an entity regardless of the form of theentity, or any option or right to acquire such position, and any rightsand/or royalties in any patent or other intellectual property.

Personal ResearchIncludes principal investigator (PI) or co-PI (if so, please specify), investi -gator, steering committee member, collaborator or consultant for pend-ing commercially-funded

Institutional or Or-ganizational (in-cluding but not lim-ited to research)

Institutional: Includes any institutional relationship between your employ-er or academic institution and a business or other entity (including gov-ernment agencies). Examples: a) If your institution is recruiting patientsfor a trial and you are a sub-investigator or co-investigator and/or if youare a Chief of Division and therefore have administrative authority and/ordirect decision-making responsibility (such as support for research grants,fellowships, and institutional supplies); b) If you are participating with anyrole into the development of guidelines promoted by scientific or busi-ness organization other than the SIE.

Organizational: Organizational competing relationships include any leader-ship or governance responsibilities or roles in another professional or oth-er nonprofit organization, whether or not remuneration is received (e.g.,Officer, Director, Trustee or other Fiduciary Role, Editor) that may have in-terests potentially competitive with the SIE.

9.4.5 Financial Value/Level of Relationship

Financial disclosures should be classified as significant, modest, or no financial relationship. A person isdeemed to have a significant interest in a business if the interest represents ownership of 5% or moreof the voting stock or share of the business entity. A relationship is considered to be modest if it is lessthan significant under the preceding definition. No financial relationship pertains to relationships forwhich you receive no monetary reimbursement.

9.5 Disclosure Timing

Relationships are disclosed 1) in writing or online in advance of the writing effort to determine eligibility ofmembers to serve on a writing committee and 2) during the document development process to ensurecomplete transparency throughout the writing and sign-off processes.Relationships that develop during the writing process must be reported to the writing group chair immedi-ately.

9.6 RWI Management

9.6.1 Writing Committee Balance (bias)

Chairs: The writing group chair is selected primarily for the competency of effectively managing thewriting group. A general working knowledge and competency in the writing topic is also necessary,but the chairperson does not necessarily have to be a leading expert in that topic. The chairpersonmust be selected to avoid significant RWI* and other relationships that could undermine the credi-bility of the writing group or its work product.Committee: A majority of writing committee members must be free of significant RWI.* At least 50%of writing committee members, plus the Chair, may have no significant RWI*. The Guideline SteeringCommittee monitors writing committee composition for RWI, as well as other potential areas of bias,such as intellectual bias/perspectives or organizational relationships potentially competitive with theSIE, and must approve each writing committee before work begins. Once chosen, authors are re-quested to avoid forming any new significant RWI during the writing effort and prior to publication inorder to maintain the RWI balance of the writing committee.

Of note, the Guideline Steering Committee also reviews writing committee balance for other issuessuch as specialty, geographic location, private practice (versus academic setting/practice), and appro-priate organizational/content expertise.

*At the discretion of the Guideline Steering Committee, certain disclosed relationships of the chair, or writing com-mittee members such as participation in government-sponsored or university-managed clinical trial or research, aswell as certain institutional/organizational and government/nonprofit relationships may be considered as NOT signif-

icant to the writing of the document.

9.7 Consensus Development

All writing committee members are invited to discuss all aspects of the document, including those forwhich they have relevant relationships with industry or other entities. The SIE values the expertise of allwriting committee members and allows open discussion to inform the writing committee’s final delibera-tion on document content. However, if one or more individuals appear to be unduly influencing the out-come of the discussion, whether they have a relevant relationship with industry related to the topic underdiscussion, a relevant relationship with another (non-industry) entity related to the topic (see above defini-tion), or other bias related to the discussion, the individual may be asked to leave the room or conferencecall during a portion or all of the discussion at the discretion of the chair.

9.7.1 External Peer Review

There are no RWI restrictions for participation in the external peer review process of a document;however, all reviewers must disclose all relevant relationships with industry and other entities relatedto the topic for publication in an appendix of the document. This promotes the opportunity for com-ment on the document from a variety of constituencies/viewpoints to inform final document content.

9.7.2 Public Disclosure of RWI

The SIE disclosure policy is cited in the published document and significant relationships with industryand other entities of authors and peer reviewers are published in a document appendix. In addition, toensure complete transparency, a hyperlink to the comprehensive RWI of each author (in effect at thetime of the writing effort) and Guideline Steering Committee member (updated in real time) is includ-ed in the document. This information resides on www.siematologia.it SIE requests an annual declaration of potential Conflict of Interest from the following individuals: members of the Strategic Committee, members of the Methodology Committee, members of the Scientific Committee. COI declarations are revised by the Strategic Committee, while COI declarations made by members of the Strategic Committee itself are revised by the Scientific Committees.

The type of COI to be declared regarding last 5 years include:

PARTECIPATION IN GUIDELINE DEVELOMPENT

o Have you been involved in the development on any of the guidelines under review (e.g.,a member of the guideline development committee)?

PERSONAL SPECIFIC INTEREST

o Have you been involved in health-care company-supported projects relevant to the guideline you are currently developing?

o Did you get economic or non-economic paybacks?

o Which type of economic payback did you get?

Consultancies

Fee-paid work

Shareholding

o Is the interest current?

PERSONAL NON-SPECIFIC INTEREST

o Have you been involved in health-care company-supported projects irrelevant to the guideline you are currently developing?

o Did you get economic or non-economic paybacks?

o Is the interest current?

NON-PERSONAL SPECIFIC INTEREST is to be declared if the department he/she is working at was involved in the last 5 years in company-sponsored projects relevant to the guideline but he/she did not get any personal revenue.

o Which kind of payback did you get from the company?

Grants

Fellowships

o Is the interest current?

NON-PERSONAL, NON-SPECIFIC INTEREST relates to payments from healthcare industry to the department he/she is working at but without any link to the guideline under construction.

PERSONAL FAMILY INTEREST either specific or non-specific

o Consultancies

o Fee-paid work

o Shareholding

Relevance of company-sponsored projects to the guideline under construction is judged by the Strategic Committee, which is allowed to request further details in order to complete the evaluation. COI declarations will be fully transparent, therefore, they will be accessible to all the members of the Guideline Project before the start of the Project itself.

10 – References

1. ADAPTE manual. www.adapte.org. version 2.0 (March 2010)

2. GRADE project. www.gradeworkinggroup.org

3. GUIDE system. www.openclinical.org

4. Ciccarese P, Caffi E, Boiocchi L, Quaglini S, Stefanelli M. A guideline management system. Medinfo. 2004;2004:28-32.

5. Micieli G, Cavallini A, Quaglini S. Guideline Compliance Improves Stroke Outcome - A Preliminary Study in 4 Districts in the Italian Region of Lombardia. Stroke 2002; 33:1341-1347.

11 – Appendix 1- AGREE checklist

The AGREE Assessment Tool asks to score each of 23 items from 1 (strongly disagree) to 7 (strongly agree).

Domain1 Scope &

purposeThe overall objective(s) of the guideline is (are) specifically describedThe health question(s) covered by the guideline is (are) specifically described.The population (patients, public, etc.) to whom the guideline is meant to apply is specifically described.

2 Stakeholder involvement

The guideline development group includes individuals fromall relevant professional groups.The views and preferences of the target population (patients, public, etc.) have been sought.The target users of the guideline are clearly defined.

3 Rigour of development

Systematic methods were used to search for evidence.

The criteria for selecting the evidence are clearly described.The strengths and limitations of the body of evidence are clearly described.The methods for formulating the recommendations are clearly described.The health benefits, side effects, and risks have been considered in formulating the recommendations.There is an explicit link between the recommendations andthe supporting evidence.The guideline has been externally reviewed by experts prior to its publication.A procedure for updating the guideline is provided.

4 Clarity of presentation

The recommendations are specific and unambiguous.

The different options for management of the condition or health issue are clearly presented.Key recommendations are easily identifiable.

5 Applicability The guideline describes facilitators and barriers to its application.The guideline provides advice and/or tools on how the recommendations can be put into practice.The potential resource implications of applying the recommendations have been considered.The guideline presents monitoring and/or auditing criteria.

6 Editorial independence

The views of the funding body have not influenced the content of the guideline.Competing interests of guideline development group members have been recorded and addressed.

Overall guideline assessment

Scoring will be calculated for each domain by normalization: scores for each n-item of the domain will be summed up and then normalized according to minimum and maximum score as below:

(SUM - n*1)/n*(7-1) = (SUM-n)/6n

12 – Appendix 2- Sources for guidelines search

Modified from ADAPTE manual.

n INTERNATIONAL GUIDELINE REPOSITORIES

1-i www.g-i-n.net Guidelines International Network (G-I-N)2-i www.guidelines.gov National Guidelines Clearinghouse (NGC)3-i www.library.nhs.uk/guidelinesfinder/4-i www.icsi.org/knowledge/ Institute for Clinical Systems Improvement

(ICSI)5-i www.uptodate.org UPTODATE

NATIONAL GUIDELINE REPOSITORIES1-n www.nzgg.org.nz/ New Zeland Guidelines Group2-n www.nhmrc.gov.au/ AU3-n www.sign.ac.uk/guidelines/index.html Scottish Intercollegiate Guidelines Network

(SIGN)4-n afssaps.sante.fr Agence Francaise de Securite Sanitaire des

Produits de Sante (AFSSAPS)5-n www.nice.org.uk/page.aspx?o=ourguidance National Institute for Clinical Evidence

(NICE)6-n mdm.ca/cpgsnew/cpgs/index.asp7-n kaypahoito.fi Finnish Medical Society Duodecim8-n doccismef.chu-rouen.fr/servlets/Simple?

Mot=recommandations+professionnelles&aff=4&tri=50&datt=1&debut=0&rechercher.x=29&rechercher.y=18

CHU de Rouen – Catalouge & Index des Sites Mèdicaux Francophones (CISMef)

9-n www.bmlweb.org/consensus.html Bibliothèque mèdicale AF Lemanissier10-n www.msss.gouv.qc.ca/sujets/prob_sante/cancer/index.php?

id=76,105,0,0,1,0Direction de la lutte contre le cancer – Ministère de la santè et des services sociauxdu Quèbec

11-n www.fnclcc.fr/-sci/sor/index.htm SOR: Standards, Options et Recommandations

12-n rnao.org Registrered Nures Association of Ontarioaezq.de Agengy for Quality in Medicine (Germany)

13-n cancercare.on.ca Cancer Care Ontario Practice Guideline Initiative

14-n www.gacguidelines.ca Ontario Guidelines Advisory Committee (GAC) Recommended Clinical Practice Guidelines

15-n www.cadth.ca Canadian Agency for Drugs and Technology in Health

16-n cancer.gov National Cancer Institute

HEMATOLOGY-ONCOLOGY SOCIETIES1-s www.siematologia.it SIE2-s www.bcshguidelines.com BCSH3-s www.leukemia-net.org ELN4-s www.sisetonline.org SISET5-s www.dgho.de

www.onkopedia-guidelines.infoDGHODGHO & OeGHO

6-s www.hematology.org ASH7-s www.nccn.org National Comprehensive Cancer Network8-s www.asco.org ASCO (US)9-s www.esmo.org ESMO10-s www.aieop.org AIEOP11-s www.ehaweb.org/eha-partners/collaborations/national-

societies/listing-of-national-societies/EHA list of European Societies

HIGH-LEVEL EVIDENCE (HTA, SR)1-e www.cochrane.org/reviews The Cochrane Library2-e www.crd.york.ac.uk/crdweb

http://www.york.ac.uk/inst/crd/crddatabases.htm#HTACentre for Reviews and Dissemination Health Technology Assessment Database

3-e www.campbellcollaboration.org The Campbell Library4-e www.eppi.ioe.ac.uk/cms/ Evidence for Policy and Practice Information

and Co-ordinating Centres

5-e health-evidence.ca6-e sante.fr/anaes/anaesparametrage.nsf/Page?

ReadForm&Section=/anaes/SiteWeb.nsf/wRubriquesID/APEH3YTFUH?OpenDocument&Defaut=y&132.203.128.28/medecine/repertoire/repertoire.asp

ANAES

7-e has-sante.fr/anaes/anaesparmetrage.nsf/Page?ReadForm&Section=/anaes/SiteWeb.nsf/wRubriquesID/APEH-3YTFUH?OpenDocument&Defaut=y&

Haute Autoritè de Santè (HAS)

8-e www.ianahta.org IANAHTA9-e euroscan.org.uk Euroscan – International Network on New

and Emerging health Technologies 10-e aquas.gencat.cat AQuAS – Agencia de Qualitat i Avauacio

Sanitaries de Catalunya11-e mdm.ca/cpgsnew/cpgs/index.asp Canadian Medical Association Infobase12-e www.fda.gov/cder/guidance/index.htm Food and Drug Administration13-e www.ema.europa.eu EMA14-e www.132.203.128.28/medecine/repertoire/repertoire.asp Directory of evidence-based Information

Web sites